Biomarker For All-cause Mortality Research Articles

Pre-hospital glycemia as a biomarker for in-hospital all-cause mortality in diabetic patients - a pilot study

BackgroundType 2 Diabetes Mellitus (T2DM) presents a significant healthcare challenge, with considerable economic ramifications. While blood glucose management and long-term metabolic target setting for home care and outpatient treatment follow established procedures, the approach for short-term targets during hospitalization varies due to a lack of clinical consensus. Our study aims to elucidate the impact of pre-hospitalization and intra-hospitalization glycemic indexes on in-hospital survival rates in individuals with T2DM, addressing this notable gap in the current literature.MethodsIn this pilot study involving 120 hospitalized diabetic patients, we used advanced machine learning and classical statistical methods to identify variables for predicting hospitalization outcomes. We first developed a 30-day mortality risk classifier leveraging AdaBoost-FAS, a state-of-the-art ensemble machine learning method for tabular data. We then analyzed the feature relevance to identify the key predictive variables among the glycemic and routine clinical variables the model bases its predictions on. Next, we conducted detailed statistical analyses to shed light on the relationship between such variables and mortality risk. Finally, based on such analyses, we introduced a novel index, the ratio of intra-hospital glycemic variability to pre-hospitalization glycemic mean, to better characterize and stratify the diabetic population.ResultsOur findings underscore the importance of personalized approaches to glycemic management during hospitalization. The introduced index, alongside advanced predictive modeling, provides valuable insights for optimizing patient care. In particular, together with in-hospital glycemic variability, it is able to discriminate between patients with higher and lower mortality rates, highlighting the importance of tightly controlling not only pre-hospital but also in-hospital glycemic levels.ConclusionsDespite the pilot nature and modest sample size, this study marks the beginning of exploration into personalized glycemic control for hospitalized patients with T2DM. Pre-hospital blood glucose levels and related variables derived from it can serve as biomarkers for all-cause mortality during hospitalization.

Serum neurofilament light levels are predictive of all-cause mortality in late middle-aged individuals.

SummaryBackgroundBlood biomarkers can offer valuable and easily accessible indicators of normal biological processes, pathogenic conditions, and responses to therapeutic interventions. Recent studies found that levels of neurofilament light chain (NfL) in the blood are associated with mortality in three European cohorts of older adults (median ages 73, 93, and 100 years). Whether similar associations exist in younger adults and in other ethnic groups is currently not known.MethodsWe utilized a cohort study that included 294 African Americans (baseline ages 49–65). Serum NfL levels were measured using a Meso Scale Discovery-based assay. Vital status was determined by matching through the National Death Index.FindingsSeventy-two participants (24.5%) died during the 14–15 years of follow up (2000–2014). Baseline serum NfL levels were significantly higher in the decedent group (86.1±65.7 pg/ml vs. 50.1±28.0 pg/ml, p < 0·001). In binomial logistic regression models adjusted for age, gender, education, baseline smoking status, BMI, and total comorbidities (0–11), serum NfL levels remained a strong predictor of all-cause mortality, and sensitivity analyses employing multiple additional covariates did not substantively change the relationship. Further, Kaplan-Meier curves based on serum NfL quartiles showed reduced survival in groups with higher serum NfL levels.InterpretationThis study found a positive association between serum NfL levels and mortality in late middle-aged and older individuals. While our findings support that serum NfL levels may be a useful biomarker for all-cause mortality, further studies are needed to understand the biological mechanisms underlying this association.FundingNational Institute on Aging, Saint Louis University.

Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis

Prognostic Value of Circulating sST2 for the Prediction of Mortality in Patients With Cardiac Light-Chain Amyloidosis.

Aims: Systemic light-chain (AL) amyloidosis is a multisystemic disorder leading to multiple organ dysfunction and mortality that is often caused by cardiac involvement. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker identified for risk stratification of heart disease. The aim of this study was to investigate the value of circulating sST2 levels in prognosis and mortality risk assessments for the AL amyloidosis population.Methods and Results: A total of 56 patients diagnosed with AL amyloidosis were enrolled in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2018. The relationships between the clinical parameters and overall survival (OS) and risk factors for disease progression were assessed. Additionally, receiver operating characteristic (ROC) curves, Kaplan–Meier analysis, and Cox hazard models were performed to explore the predictive value of sST2 in mortality rates. We found that the median OS of all patients was 7.3 [interquartile range (IQR) 4.4, 15.9] months. The median baseline sST2 level was 12.2 (IQR 5.1, 31.1) ng/ml, and the sST2 high group had more severe patients with a higher Mayo stage. In the ROC analysis, the area under the curve (AUC) was 0.728 [95% confidence interval (CI) 0.603–0.853] for sST2 to predict the outcomes of AL amyloidosis patients, and the optimal cutoff value was 12.34 ng/ml (sensitivity 80.2%, specificity 61.1%). Moreover, in multivariate Cox proportional hazards regression analysis, sST2 acted as an independent predictor of poor functional outcome in patients with AL amyloidosis.Conclusion: In AL amyloidosis patients, sST2 was a strong and independent prognostic biomarker for all-cause mortality, providing complementary prognostic information of a novel scoring system for risk stratification.

Associations Between the Serum Metabolome and All-Cause Mortality Among African Americans in the Atherosclerosis Risk in Communities (ARIC) Study.

Early and accurate identification of people at high risk of premature death may assist in the targeting of preventive therapies in order to improve overall health. To identify novel biomarkers for all-cause mortality, we performed untargeted metabolomics in the Atherosclerosis Risk in Communities (ARIC) Study. We included 1,887 eligible ARIC African Americans, and 671 deaths occurred during a median follow-up period of 22.5 years (1987-2011). Chromatography and mass spectroscopy identified and quantitated 204 serum metabolites, and Cox proportional hazards models were used to analyze the longitudinal associations with all-cause and cardiovascular mortality. Nine metabolites, including cotinine, mannose, glycocholate, pregnendiol disulfate, α-hydroxyisovalerate, N-acetylalanine, andro-steroid monosulfate 2, uridine, and γ-glutamyl-leucine, showed independent associations with all-cause mortality, with an average risk change of 18% per standard-deviation increase in metabolite level (P < 1.23 × 10(-4)). A metabolite risk score, created on the basis of the weighted levels of the identified metabolites, improved the predictive ability of all-cause mortality over traditional risk factors (bias-corrected Harrell's C statistic 0.752 vs. 0.730). Mannose and glycocholate were associated with cardiovascular mortality (P < 1.23 × 10(-4)), but predictive ability was not improved beyond the traditional risk factors. This metabolomic analysis revealed potential novel biomarkers for all-cause mortality beyond the traditional risk factors.

Longitudinal Electrocardiographic Evaluation of Dogs with Degenerative Mitral Valve Disease

BackgroundIncreased heart rate (HR) and decreased heart rate variability (HRV) are evident in some dogs with degenerative mitral valve disease (DMVD).ObjectivesEvaluation of the factors influencing HR and HRV (assessed by the vasovagal tonus index; VVTI) and their change over time in dogs with DMVD.AnimalsClient‐owned dogs (n = 257) with DMVD recruited from first opinion practice.MethodsProspective longitudinal follow‐up at six‐monthly intervals of dogs with DMVD. Dogs followed up for at least 18 months (n = 102) were grouped according to their outcome as dogs dying/euthanized because of cardiac disease (n = 28; Group 1), noncardiac disease (n = 40; Group 2) and dogs alive (n = 34; Group 3). HR and VVTI were measured on 1‐minute ECG recordings. Repeated measures linear models were constructed to investigate the factors that influence HR and VVTI and their changes over time.ResultsHeart rate and VVTI were affected by disease severity and were different in Cavaliers compared to other breeds. Group 1 and Group 2 dogs underwent an increase in HR and decrease in VVTI, evident at least 18 months before death. Group 1 had a further decrease in VVTI followed by an increase in HR approximately 1 year and 6 months before death, respectively.Conclusions and Clinical ImportanceDogs with DMVD have an increase in HR and decrease in HRV over a year before death, with greater changes in those dogs dying/euthanized because of cardiac disease. Both HR and VVTI can potentially be regarded as biomarkers for all‐cause mortality.

THE INFLAMMATORY BIOMARKER YKL-40 AS A NEW PROGNOSTIC MARKER FOR ALL-CAUSE MORTALITY IN PATIENTS WITH HEART FAILURE

a b s t r a c t Background: Despite progress in management of patients with heart failure (HF) these patients still have a poor prognosis. We tested the hypothesis whether the inflammatory biomarker YKL-40 alone or in com- bination with high-sensitivity C-reactive protein (hs-CRP) and/or N-terminal-pro-B natriuretic peptide (NT-proBNP) could be a new prognostic biomarker for all-cause mortality in patients with HF. Methods and results: A total of 717 of the 1000 patients with severe left ventricular systolic dysfunction included in the EchoCardiography and Heart Outcome Study were included in Denmark and had blood sample available for serum YKL-40 determination. Mean age of patients was 70 years, and 73% were male. During the 7 years follow-up period 458 patients died. Patients were categorised according to serum YKL- 40 at entry into four quartiles: quartile I with median serum YKL-40 = 60 g/L (5-95% Confidence interval (CI): 30-82), quartile II: YKL-40 = 107 g/L (CI: 86-132), quartile III: YKL-40 = 169 g/L (CI: 142-221), and quartile IV: YKL-40 = 286 g/L (CI: 230-770). Hazard ratios for all-cause mortality were with quartile I as reference 1.33 (CI: 0.99-1.80), 1.35 (CI: 0.99-1.82), and 1.54 (CI: 1.14-2.08) for serum YKL-40 II to IV quartiles, respectively following multivariable adjustment for cardiovascular risk factors (age, left ventricular ejection fraction, gender, history of heart failure, ischemic heart disease, chronic pulmonary disease, diabetes mellitus, stroke, hypertension, NT-proBNP, hs-CRP, and renal function). Conclusion: Serum YKL-40 is significantly associated with all-cause mortality in patients with HF and could potentially be a new prognostic biomarker in these patients. © 2011 Elsevier GmbH. All rights reserved.